Idera Announces Presentation of Positive Data from Phase 2 Trial of TLR 7 and 9 Antagonist in Patients with Moderate-to-Severe

Idera Announces Presentation of Positive Data from Phase 2 Trial of TLR 7
and 9 Antagonist in Patients with Moderate-to-Severe Plaque Psoriasis
PASI Score Improvements Correlated with Downregulation of IL-17 Pathway
IID 2013
Business Wire
CAMBRIDGE, Mass. -- May 8, 2013
Idera Pharmaceuticals (NASDAQ: IDRA) today announced presentation of data from
its randomized, double-blind, placebo-controlled Phase 2 trial that showed
improvements from baseline of up to 90% in Psoriasis Area Severity Index
(PASI) scores in patients with moderate to severe plaque psoriasis following
four weeks of treatment with the Toll-like Receptor (TLR) antagonist IMO-3100.
Additionally, analysis of biopsy samples collected from patients during the
Phase 2 trial indicated that PASI score improvements were associated with
significant improvement of psoriasis disease-associated gene profile,
including downregulation of activated genes in the IL-17 pathway, which is
central to the pathogenesis of psoriasis. Treatment with IMO-3100 was well
tolerated, with no treatment-related discontinuations. The presentation
entitled “IMO-3100, an antagonist of Toll-like receptor (TLR) 7 and 9,
demonstrates clinical activity in psoriasis patients with 4 weeks of treatment
in a Phase 2a trial” was made by Alexa Kimball M.D., M.P.H., Vice Chair,
Department of Dermatology at Massachusetts General Hospital, Boston, and an
investigator in the trial, at the International Investigative Dermatology
meeting in Edinburgh, Scotland May 8^th through 13^th, 2013.
“TLR antagonism provides a novel mechanism of action for the potential
treatment of patients with moderate to severe plaque psoriasis. Clinical
activity demonstrated in this four-week proof-of-concept trial encourages
further development of TLR antagonists over longer treatment periods,” said
Dr. Kimball.
“We are very pleased that the clinical improvements observed in psoriasis
patients treated with IMO-3100 for four weeks correlated with the proposed
mechanism of action for TLR antagonism in autoimmune diseases,” said Robert
Arbeit, MD, VP of Clinical Development at Idera. “Our next step will be a
12-week Phase 2 clinical trial in patients with psoriasis, which we expect
will enable us to evaluate the continued trajectory of PASI score improvement
over the 12-week treatment period and maximize the clinical benefit of the
treatment. We plan to conduct this 12-week Phase 2 trial with IMO-8400, an
antagonist of TLRs 7, 8, and 9, and to initiate the trial during the second
quarter of 2013.”
Data from the Phase 2 Trial
The objectives of the Phase 2 trial of IMO-3100 were to evaluate the safety
and tolerability and to evaluate the clinical activity of TLR antagonism in
patients with psoriasis after four weeks of treatment. Top-line data from this
trial was announced in December 2012. Data presented from this trial include:
Safety:
*Treatment with IMO-3100 was well tolerated at both dose levels studied
*There were no treatment-related discontinuations or changes in laboratory
parameters
Clinical Activity:
*On day 57, 48% of patients treated with either dose of IMO-3100 (12 of 25)
demonstrated statistically significant improvements of 35% to 90% from
baseline PASI scores compared with 0 of 12 in the placebo cohort (p<0.005)
*Rapid improvement in PASI scores was observed in IMO-3100 treated patients
compared to placebo-treated patients; Improvement in PASI was sustained
through five weeks after the last dose
*The pre-specified clinical endpoint of reduction in PASI score at day 29
was achieved with statistical significance in the 0.16 mg/kg cohort
(p<0.02 compared to placebo) but not in the 0.32 mg/kg cohort
*PASI 50 was achieved in 7 of 25 patients treated with IMO-3100 (3 of 12 at
0.16 mg/kg and 4 of 13 at 0.32 mg/kg), compared to 0 of 12 placebo treated
patients (p<0.05); PASI 75 was achieved in 1 patient in each IMO-3100
cohort during the trial period
*The pre-specified clinical endpoint of improvement in induration, a
measure of plaque thickness, at day 29 was achieved with statistical
significance in the 0.16 mg/kg cohort (p<0.02) compared to placebo-treated
patients
Mechanism of Action Based on Analysis of Skin Biopsies:
*Median change in epidermal thickness (the histologically defined primary
endpoint of the trial) was -6.4% in IMO-3100 treated patients compared to
+7.7% in placebo treated patients, representing a favorable, but not
statistically significant, trend. A known limitation of skin biopsies
after four weeks of treatment is that psoriatic plaques do not resolve in
a uniform fashion, and therefore, biopsies may not provide a
representative sampling of lesions (ref: Ann Rheum Dis 2005;64:65-68)
*Representative patients treated with IMO-3100 showed K16 staining (marker
of keratinocyte proliferation) reverting toward normal and decreasing
infiltrates of CD3+ lymphocytes and CD11c+ cells
*DNA microarray analysis of biopsies from the IMO-3100 treated patients
compared to placebo treated patients (n=6 each) showed significant
improvement (p<10^-6) in psoriasis disease-associated genes (Tian et al,
PLoS ONE, Sep 2012) and of genes unique to the IL-17 pathway, which is
central to the pathogenesis of psoriasis. Detailed data will be presented
at a future scientific meeting.
About the Phase 2 Trial in Psoriasis
The Phase 2 trial was a randomized, double-blind, placebo-controlled trial of
IMO-3100 in patients with moderate-to-severe plaque psoriasis. In the trial,
44 patients at 11 centers in the United States were randomized to receive
IMO-3100 monotherapy at 0.16 or 0.32 mg/kg or placebo by subcutaneous
injection once weekly for four weeks. Patients were treated on Days 1, 8, 15,
and 22, and were monitored during a follow-up period through approximately Day
57. Assessments of safety were performed throughout the trial. Psoriasis Area
Severity Index (PASI) scores were monitored during the treatment period on
Days 1, 15, and 29, and during the follow-up period on Days 36 and 57. Skin
biopsies were collected prior to treatment on Day 1 and on Day 29. The
biopsies were analyzed by James Krueger, M.D., Ph.D., at The Rockefeller
University, New York, for treatment-related changes in epidermal thickness,
Immunology markers, and gene expression.
Next Step in Autoimmune Disease Program
Based on the clinical activity of IMO-3100 observed in patients with
psoriasis, and the comparative profiles of IMO-3100 and IMO-8400, including
the inhibition of TLR8 by IMO-8400, Idera has determined that the next step is
to conduct a Phase 2 clinical trial of IMO-8400 in patients with psoriasis
with a treatment period of up to 12 weeks. In this trial, 32 patients would be
randomized to receive weekly doses for up to 12 weeks at one of three dose
levels of IMO-8400 or placebo. This Phase 2 protocol has been approved by the
Centrale Commisse Mensgebonden Onderzoek of the Netherlands. Idera anticipates
initiating enrollment under this protocol during the second quarter of 2013.
About TLRs and Idera's Pipeline
Toll-like Receptors (TLRs) play a key role in inflammation and immunity. Idera
is developing compounds targeted to TLRs 3, 7, 8, and 9, which are expressed
in different cells and serve unique functions. Using its chemistry-based
approach, Idera has created novel drug candidates that modulate immune
responses through either activation or inhibition of specific TLRs. In
autoimmune diseases, immune complexes containing self-nucleic acids activate
TLRs 7, 8, and 9 and induce multiple cytokines that cause further damage to
the body's own tissues and organs, thereby releasing more self-nucleic acids.
Inhibition of specific TLRs may be useful in treating autoimmune diseases,
such as systemic lupus erythematosus (SLE), psoriasis, and rheumatoid
arthritis, by blocking the induction of multiple cytokines and signaling
pathways. Idera's clinical candidates for application in autoimmune diseases
are IMO-3100, an antagonist of TLR7 and TLR9, and IMO-8400, an antagonist of
TLRs 7, 8, and 9.
About Psoriasis
Psoriasis is a systemic immune-mediated disorder, characterized by
inflammatory skin and joint manifestations. The most common form, plaque
psoriasis, appears as raised, red patches covered with a silvery white buildup
of dead skin cells. Psoriasis can occur on any part of the body and is
associated with other serious health conditions, such as diabetes, heart
disease and depression.
Psoriasis is the most prevalent autoimmune disease in the U.S., according to
the National Psoriasis Foundation, affecting as many as 7.5 million Americans.
About IID 2013
International Investigative Dermatology 2013 (IID 2013) brings together the
European Society for Dermatological Research (ESDR), Japanese Society for
Investigative Dermatology (JSID) and Society for Investigative Dermatology
(SID) to share the latest information on cutaneous biology and skin diseases.
IID 2013 takes places in Edinburgh, Scotland, from May 8th to 13th. For more
information, visit www.iid2013.org.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals applies its proprietary Toll-like receptor (TLR) drug
discovery platform to create immunomodulatory drug candidates and has a
clinical development program in autoimmune diseases. Additionally, Idera has a
collaboration with Merck & Co. for the use of TLR-targeted candidates as
vaccine adjuvants for cancer, infectious diseases and Alzheimer’s disease. For
more information, visit http://www.iderapharma.com.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera
Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For
this purpose, any statements contained herein that are not statements of
historical fact may be deemed to be forward-looking statements. Without
limiting the foregoing, the words "believes," "anticipates," "plans,"
"expects," "estimates," "intends," "should," "could," "will," "may," and
similar expressions are intended to identify forward-looking statements. There
are a number of important factors that could cause Idera's actual results to
differ materially from those indicated by such forward-looking statements,
including whether Idera’s cash resources will be sufficient to fund the
Company’s continuing operations and the further development of the Company’s
autoimmune disease program; whether results obtained in preclinical studies
and early clinical trials, such as the results from the Phase 2 trial referred
to in this release, will be indicative of results obtained in future clinical
trials; whether products based on Idera's technology will advance into or
through the clinical trial process on a timely basis or at all and receive
approval from the United States Food and Drug Administration or equivalent
foreign regulatory agencies; whether, if the Company's products receive
approval, they will be successfully distributed and marketed; whether the
Company will be able to license any of its TLR target candidates on a timely
basis or at all; whether the Company's collaboration with Merck & Co, Inc.,
will be successful; whether the patents and patent applications owned or
licensed by the Company will protect the Company's technology and prevent
others from infringing it; and such other important factors as are set forth
under the caption "Risk Factors" in Idera's Annual Report on Form 10-K for the
year ended December 31, 2012 which important factors are incorporated herein
by reference. Idera disclaims any intention or obligation to update any
forward-looking statements.
Contact:
Idera Pharmaceuticals, Inc.
Lou Arcudi, 617-679-5517
larcudi@iderapharma.com